Histones are abundant and highly essential eukaryotic proteins that are basic in nature. Two molecules of each of the four core histones, H2A, H2B, H3 and H4, constitute the histone octamer, around which 147 base pairs of DNA are wrapped to form the nucleosome core particle. The core particle is the fundamental repeating unit of eukaryotic chromatin. A linker histone, also known as histone H1, is present in higher eukaryotes and seals two full turns of the DNA to form the complete nucleosome. The major function of nucleosome was appreciated early—this nucleosomal structure is repeated until the entire genomic DNA is packaged into chromatin fibers. The chromatin fibers undergo further compaction to form chromosomes, the basic units of genetic information in all living eukaryotes. In last decade or so it became apparent that histones and chromatin structure regulate access to the information contained within the DNA. And this information plays a crucial role in majority of cellular and metabolic processes e.g. transcription, replication, recombination and DNA damage and repair. This truly has opened the door for the deeper understanding of how histone modification and subsequent changes in chromatin regulates normal human physiology. But the most critical issue is how this process is involved in various diseases e.g. cancer, diabetes and aging.
It is becoming clear that post-translational modifications of histones are important. So far, the core histones have been shown to be phosphorylated, acetylated, methylated, sumoylated, ribosylated and ubiquitylated at various amino acid residues, forming a ‘histone code’ or ‘epigenetic code’. The histone code suggests that histone modifications not only alter the affinity of histones for DNA but importantly act as recognition or binding sites for various factors or proteins to assemble at the site of modification. This results in relay of information that leads to initiation or suppression of specific cellular event or process. Interestingly, the epigenetic code also results in crosstalk between the different modifications, e.g. phosphorylation, methylation, acetylation and ubiquitination.
Histone modifications are the epigenetic changes. It is now known that in addition to genetic defects, epigenetic defects can also result in disease. Epigenetics is also thought to play a major role in the pathogenesis of common, multifactorial disorders. For example, there is evidence suggesting that the primary (idiopathic) disorders like schizophrenia and bipolar disorder are epigenetic defects rather than genetic defects. Epigenetic factors have also been shown to be involved in aging, in rare monogenic disorders like fragile-X mental retardation, and in lymphomas.